Colorectal cancer mortality ranks second among all causes of malignant death in industrialized nations. Recognition and curative treatment of precursor (premalignant) adenomas and localized cancers is possible with early detection.
Currently fecal occult blood testing is a widely utilized screening tool for the early detection of colorectal neoplasia, but suffers from several disadvantages. Fecal blood testing measures an ambiguous marker for colorectal neoplasia--hemoglobin--and tests for hemoglobin in stool samples have proved to be neither specific nor sufficiently sensitive. Recent reports indicate that fecal blood testing fails to detect over 70 percent of pre-malignant polyps. Colorectal neoplasms bleed intermittently, and thus fecal occult blood is not a reliable marker for colorectal neoplasia. Moreover, there are many causes of gastrointestinal bleeding unrelated to colorectal neoplasia, resulting in a very high level of false positives using the fecal occult blood screening method. False positives result in unnecessary and costly follow-up procedures such as colonoscopy.
In terms of simplicity, however, stool testing approaches the ideal for colorectal cancer screening; it is non-invasive, has a low unit cost, generates reasonably high compliance, and reflects the entire colorectal surface. A specific and sensitive stool screening test for colorectal neoplasia would thus be extremely valuable.
Exfoliated dysplastic epithelial cells represent a possible stool marker for colon cancer. Such cells obtained from lavage effluents have been shown to be reliable markers of colorectal cancer, but specimen collection required the invasive technique of colorectal purgation, limiting the clinical utility of this approach. Recently, a density gradient centrifugation technique was developed to collect sloughed colonocytes from routine stool samples. This technique, however, is time-consuming and technically complex, and therefore does not allow for an efficient and selective recovery of colorectal epithelial cells, is not amenable to large volume processing, and thus is not useful as a stool screening technique of the type currently needed.